The frequency of interleukin-1ß-producing monocytes is significantly associated with varicella-zoster responses of nursing home residents.

Previous studies have demonstrated that the status of the T cell compartment and inflammation-related factors are associated with the immunogenicity of the varicella-zoster virus (VZV) vaccine in older adults; however, little is known about the roles of other immune cell subsets known to influence the generation and maintenance of immunological memory. Responses to a live-attenuated VZV vaccine were studied in relation to peripheral blood mononuclear cell (PBMC) composition and function in a sample of 30 nursing home residents (aged 80-99 years). Interferon-gamma enzyme-linked immunospot (ELISPOT) was used to measure VZV responses at baseline and 6 weeks following vaccination, and associations were sought with the frequencies of monocytes and T, B and natural killer (NK) cells and the production and secretion of cytokines following their ex-vivo stimulation with different agents. While only the frequency of interleukin (IL)-6+ CD14+ monocytes was inversely associated with post-vaccination VZV response, amounts of IL-1ß, IL-10, IL-17A and tumour necrosis factor (TNF) secreted by PBMCs and the frequency of IL-1ß+ CD14+ monocytes was positively correlated with pre-vaccination VZV response. Furthermore, both bivariate correlation and causal mediation analyses supported the notion that IL-1ß+ CD14+ monocytes were significant mediators of the associations between IL-1ß and TNF secretion by PBMCs and pre-vaccination VZV responses. Our findings implicate a strong cytokine response mediated by inflammatory IL-1ß+ monocytes in coordinating responses of long-lived VZV-reactive memory T cells, but with an opposing effect of IL-6+ CD14+ monocytes. Whether monocyte status promotes or inhibits the induction and/or maintenance of these memory T cells later in life has yet to be determined.

Exogenous interleukin-2 can rescue in-vitro T cell activation and proliferation in patients with a novel capping protein regulator and myosin 1 linker 2 mutation.

Capping protein regulator and myosin 1 linker 2 (CARMIL2) deficiency is characterized by impaired T cell activation, which is attributed to defective CD28-mediated co-signaling. Herein, we aimed to analyze the effect of exogenous interleukin (IL)-2 on in-vitro T cell activation and proliferation in a family with CARMIL2 deficiency. This study included four children (one male and three females; aged 2·5-10 years at presentation). The patients presented with inflammatory bowel disease and recurrent viral infections. Genetic analysis revealed a novel homozygous 25-base pairs deletion in CARMIL2. Immunoblotting demonstrated the absence of CARMIL2 protein in all four patients and confirmed the diagnosis of CARMIL2 deficiency. T cells were activated in-vitro with the addition of IL-2 in different concentrations. CD25 and interferon (IFN)-γ levels were measured after 48 h and 5 days of activation. CD25 surface expression on activated CD8+ and CD4+ T cells was significantly diminished in all patients compared to healthy controls. Additionally, CD8+ T cells from all patients demonstrated significantly reduced IFN-γ production. When cells derived from CARMIL2-deficient patients were treated with IL-2, CD25 and IFN-γ production increased in a dose-dependent manner. T cell proliferation, as measured by Cell Trace Violet, was impaired in one patient and it was also rescued with IL-2. In conclusion, we found that IL-2 rescued T cell activation and proliferation in CARMIL2-deficient patients. Thus, IL-2 should be further studied as a potential therapeutic modality for these patients.

Expanding the phenotype of CRB2 mutations - A new ciliopathy syndrome?

Recessive CRB2 mutations were recently reported to cause both steroid resistant nephrotic syndrome and prenatal onset ventriculomegaly with kidney disease. We report two Ashkenazi Jewish siblings clinically diagnosed with ciliopathy. Both presented with severe congenital hydrocephalus and mild urinary tract anomalies. One affected sibling also has lung hypoplasia and heart defects. Exome sequencing and further CRB2 analysis revealed that both siblings are compound heterozygotes for CRB2 mutations p.N800K and p.Gly1036Alafs*43, and heterozygous for a deleterious splice variant in the ciliopathy gene TTCB21. CRB2 is a polarity protein which plays a role in ciliogenesis and ciliary function. Biallelic CRB2 mutations in animal models result in phenotypes consistent with ciliopathy. This report expands the phenotype of CRB2 mutations to include lung hypoplasia and uretero-pelvic renal anomalies, and confirms cardiac malformation as a feature. We suggest that CRB2-associated disease is a new ciliopathy syndrome with possible digenic/triallelic inheritance, as observed in other ciliopathies. Clinically, CRB2 should be assessed when ciliopathy is suspected, especially in Ashkenazi Jews, where we found that p.N800K carrier frequency is 1 of 64. Patients harboring CRB2 mutations should be tested for the complete range of ciliopathy manifestations.

Influence of age on retinochoroidal healing processes after argon photocoagulation in C57bl/6j mice.

PURPOSE: To analyze the influence of age on retinochoroidal wound healing processes and on glial growth factor and cytokine mRNA expression profiles observed after argon laser photocoagulation. METHODS: A cellular and morphometric study was performed that used 44 C57Bl/6J mice: 4-week-old mice (group I, n=8), 6-week-old mice (group II, n=8), 10-12-week-old mice (group III, n=14), and 1-year-old mice (group IV, n=14). All mice in these groups underwent a standard argon laser photocoagulation (50 microm, 400 mW, 0.05 s). Two separated lesions were created in each retina using a slit lamp delivery system. At 1, 3, 7, 14, 60 days, and 4 months after photocoagulation, mice from each of the four groups were sacrificed by carbon dioxide inhalation. Groups III and IV were also studied at 6, 7, and 8 months after photocoagulation. At each time point the enucleated eyes were either mounted in Tissue Tek (OCT), snap frozen and processed for immunohistochemistry or either flat mounted (left eyes of groups III and IV). To determine, by RT-PCR, the time course of glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF), and monocyte chemotactic protein-1 (MCP-1) gene expression, we delivered ten laser burns (50 microm, 400 mW, 0.05 s) to each retina in 10-12-week-old mice (group III', n=10) and 1-year-old mice (group IV', n=10). Animals from Groups III' and IV' had the same age than those from Groups III and IV, but they received ten laser impacts in each eye and served for the molecular analysis. Mice from Groups III and IV received only two laser impacts per eye and served for the cellular and morphologic study. Retinal and choroidal tissues from these treated mice were collected at 16 h, and 1, 2, 3, and 7 days after photocoagulation. Two mice of each group did not receive photocoagulation and were used as controls. RESULTS: In the cellular and morphologic study, the resultant retinal pigment epithelium interruption expanse was significantly different between the four groups. It was more concise and smaller in the oldest group IV (112.1 microm+/-11.4 versus 219.1 microm+/-12.2 in group III) p<0.0001 between groups III and IV. By contrast, while choroidal neovascularization (CNV) was mild and not readily identifiable in group I, at all time points studied, CNV was more prominent in the (1-year-old mice) Group IV than in the other groups. For instance, up to 14 days after photocoagulation, CNV reaction was statistically larger in group IV than in group III ((p=0.0049 between groups III and IV on slide sections and p<0.0001 between the same groups on flat mounts). Moreover, four months after photocoagulation, the CNV area (on slide sections) was 1,282 microm(2)+/-90 for group III and 2,999 microm(2)+/-115 for group IV (p<0.0001 between groups III and IV). Accordingly, GFAP, VEGF, and MCP-1 mRNA expression profiles, determined by RT-PCR at 16 h, 1, 2, 3, and 7 days postphotocoagulation, were modified with aging. In 1-year-old mice (group IV), GFAP mRNA expression was already significantly higher than in the younger (10-12 week) group III before photocoagulation. After laser burns, GFAP mRNA expression peaked at 16-24 h and on day 7, decreasing thereafter. VEGF mRNA expression was markedly increased after photocoagulation in old mice eyes, reaching 2.7 times its basal level at day 3, while it was only slightly increased in young mice (1.3 times its level in untreated young mice 3 days postphotocoagulation). At all time points after photocoagulation, MCP-1 mRNA expression was elevated in old mice, reaching high levels of expression at 16 h and day 3 respectively. CONCLUSIONS: Our results were based on the study of four different age groups and included not only data from morphological observations but also from a molecular analysis of the various alterations of cytokine signaling and expression. One-year-old mice demonstrated more extensive CNV formation and a slower pace of regression after laser photocoagulation than younger mice. These were accompanied by differences in growth factors and cytokine expression profiles indicate that aging is a factor that aggravates CNV. The above results may provide some insight into possible therapeutic strategies in the future.

Tuning of an active photonic crystal cavity by an hybrid silica/silicon near-field probe.

The influence of a near-field tip on the spectral characteristics of a resonant mode of an active photonic crystal micro-cavity was investigated. The wavelength shift of the mode was theoretically and experimentally demonstrated and evaluated as a function of the nature and the position of the tip above the cavity. Experiment showed that the shift induced is ten times higher with a Si-coated silica probe than with a bare silica tip: a shift until 2 nm was reached with Si-coated tip whereas the shift with bare silica tip is in the range of the tenth of nanometer, for wavelengths around 1,55 microm.

Disrupted Iron Storage in Dental Fluorosis.

Enamel formation and quality are dependent on environmental conditions, including exposure to fluoride, which is a widespread natural element. Fluoride is routinely used to prevent caries. However, when absorbed in excess, fluoride may also lead to altered enamel structural properties associated with enamel gene expression modulations. As iron plays a determinant role in enamel quality, the aim of our study was to evaluate the iron metabolism in dental epithelial cells and forming enamel of mice exposed to fluoride, as well as its putative relation with enamel mechanical properties. Iron storage was investigated in dental epithelial cells with Perl's blue staining and secondary ion mass spectrometry imaging. Iron was mainly stored by maturation-stage ameloblasts involved in terminal enamel mineralization. Iron storage was drastically reduced by fluoride. Among the proteins involved in iron metabolism, ferritin heavy chain (Fth), in charge of iron storage, appeared as the preferential target of fluoride according to quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry analyses. Fluorotic enamel presented a decreased quantity of iron oxides attested by electron spin resonance technique, altered mechanical properties measured by nanoindentation, and ultrastructural defects analyzed by scanning electron microscopy and energy dispersive x-ray spectroscopy. The in vivo functional role of Fth was illustrated with Fth+/- mice, which incorporated less iron into their dental epithelium and exhibited poor enamel quality. These data demonstrate that exposure to excessive fluoride decreases ameloblast iron storage, which contributes to the defective structural and mechanical properties in rodent fluorotic enamel. They raise the question of fluoride's effects on iron storage in other cells and organs that may contribute to its effects on population health.

New steps in the control of canine rabies in India.

In India, about 20,000 people die of rabies every year. The dog is the main reservoir and transmitter of the disease. A pilot rabies control programme was launched in five Indian federal states in February, 2007. This initiative is led by the Animal Welfare Board of India (AWBI) federating many animal welfare organizations and the Ministry of Agriculture. It aims at creating a "Rabies Free India." The programme combines parenteral vaccination of accessible owned and stray dogs, spaying/neutering followed by parenteral vaccination and oral vaccination of inaccessible dogs. The freeze-dried vaccine SAG2, including the bait casing, was registered in India following successful evaluation of vaccine-bait safety and efficacy (by survival after virulent challenge) in captive Indian stray dogs in the Bhopal High Security Animal Disease Laboratory. Furthermore, bait acceptance was tested under both experimental and field conditions.

Optical tweezing using tunable optical lattices along a few-mode silicon waveguide.

Fourteen years ago, optical lattices and holographic tweezers were considered as a revolution, allowing for trapping and manipulating multiple particles at the same time using laser light. Since then, near-field optical forces have aroused tremendous interest as they enable efficient trapping of a wide range of objects, from living cells to atoms, in integrated devices. Yet, handling at will multiple objects using a guided light beam remains a challenging task for current on-chip optical trapping techniques. We demonstrate here on-chip optical trapping of dielectric microbeads and bacteria using one-dimensional optical lattices created by near-field mode beating along a few-mode silicon nanophotonic waveguide. This approach allows not only for trapping large numbers of particles in periodic trap arrays with various geometries, but also for manipulating them via diverse transport and repositioning techniques. Near-field mode-beating optical lattices may be readily implemented in lab-on-a-chip devices, addressing numerous scientific fields ranging from bio-analysis to nanoparticle processing.

Ultra-High Q/V Fabry-Perot microcavity on SOI substrate.

We experimentally demonstrate an ultra high Q/V nanocavity on SOI substrate. The design is based on modal adaptation within the cavity and allows to measure a quality factor of 58.000 for a modal volume of 0.6(lambda/n)(3) . This record Q/V value of 10(5) achieved for a structure standing on a physical substrate, rather than on membrane, is in very good agreement with theoretical predictions also shown. Based on these experimental results, we show that further refinements of the cavity design could lead to Q/V ratios close to 10(6).

Influence of the intercalated cations on the surface energy of montmorillonites: consequences for the morphology and gas barrier properties of polyethylene/montmorillonites nanocomposites.

Organically modified montmorillonites obtained by cation exchange from the same natural layered silicate were studied. The surface properties of the pristine and a series of organically modified clays were determined by inverse gas chromatography and the water adsorption mechanisms were studied by a gravimetric technique coupled with a microcalorimeter. A significant increase of the specific surface area, a decrease of the water adsorption, and a decrease of the dispersive component of the surface energy were observed when the sodium cations of the natural montmorillonite were exchanged for a quaternary ammonium. Slighter differences in surface properties were observed, on the other hand, between the different types of organically modified montmorillonites. Indeed, similar dispersive components of the surface energy were determined on the organoclays. Nevertheless, the specific surface area increased in the range 48-80 m(2)/g with increasing d-spacing values and the presence of specific groups attached to the quaternary ammonium, such as phenyl rings or hydroxyl groups, led to some specific behaviors, i.e., a more pronounced base character and a higher water adsorption at high activity, respectively. Differences in interlayer cation chain organization, denoted as crystallinity, were also observed as a function of the nature of the chains borne by the quaternary ammonium. In a later step, polyethylene-based nanocomposites were prepared with those organically modified montmorillonites. The clay dispersion and the barrier properties of the nanocomposites were discussed as a function of the montmorillonite characteristics and of the matrix/montmorillonite interactions expected from surface energy characterization.

Expression of retinoid receptor genes and proteins in non-small-cell lung cancer.

BACKGROUND: Retinoids can suppress carcinogenesis in high-risk non-neoplastic bronchial lesions and can reduce the risk of second primary non-small-cell lung cancer (NSCLC). The effects of retinoids are mediated by nuclear receptors, i.e., the retinoic acid receptors (RARalpha, RARbeta, and RARgamma) and the retinoid X receptors (RXRalpha, RXRbeta, and RXRgamma). We investigated whether abnormalities in the in vivo expression of retinoid receptors are observed in NSCLC. METHODS: Expression of retinoid receptors in paired specimens of normal and cancerous tissues from the lungs of 76 patients with NSCLC was studied by use of antiretinoid receptor antibodies (except those against RXRgamma) and immunohistochemistry. RAR messenger RNAs were analyzed by use of in situ hybridization and by reverse transcription-polymerase chain reaction (RT-PCR). Samples were also studied for loss of heterozygosity (LOH) at chromosome 3p24. All P values are two-sided. RESULTS: All studied receptors were expressed in normal lung cells and in high- risk non-neoplastic lesions. In tumor cells, overexpression of RXRalpha and RARalpha was frequently observed. In contrast, RXRbeta expression decreased in 18% of the tumor specimens. Furthermore, there was a marked decrease in the expression of RARbeta in 63% of the tumors (P<.0001). Decreased expression of RARgamma was observed by RT-PCR in 41% of the tumors (P<.0001). LOH at 3p24 was observed in 41% of the tumor specimens from informative patients and in 20% of the non-neoplastic lesions. CONCLUSIONS: Expression of RARalpha and RXRalpha is either normal or elevated in NSCLC. In contrast, a large percentage of tumors show a marked decrease in the expression of RARbeta, RARgamma, and RXRbeta as well as a high frequency of LOH at 3p24, which was also observed in non-neoplastic lesions. These data suggest that altered retinoid receptor expression may play a role in lung carcinogenesis.

Retinoic acid receptor and retinoid X receptor alterations in lung cancer precursor lesions.

Smoking prevention will decrease lung cancer incidence in time. However, early detection would improve lung cancer prognosis in subjects at risk provided that specific markers could be identified. We previously reported that retinoic acid receptor (RAR) and retinoid X receptor (RXR) expression was altered in lung tumors. RAR-beta gene status could be derived from corresponding allelotyping and immunohistochemistry data. We now report the continued study on lung cancer precursor lesions. Fluorescence PCR-based assays were used for allelotyping at the RAR/RXR loci of: (a) 66 lung precursor lesions found at the free resection margins of 41 patients undergoing surgery for lung cancer (+ 31 paired tumors); and (b) bronchial cells also found at the free resection margins from 16 current and 8 never smokers operated on for noncancerous diseases. Three microsatellites located at 3p14-21 and 9p21 were also used for interwork comparison. Immunohistochemistry was additionally performed to evaluate P53 and RAR-beta expression in precursor lesions. Chi2 tests showed significant differences (P < 0.05) when comparing the results obtained from never smokers, smokers, squamous metaplasia, dysplasia + in situ carcinoma, and tumors. Microsatellite changes occurred frequently in all samples, but without specificity for any group (P < 0.08-0.52). They were globally correlated with tobacco exposure (P < 0.04), for which the RAR-gamma marker appeared as a preferential target (P < 0.004). Few reparation error phenotypes were observed, mostly at the RXR-alpha and RXR-gamma markers for which combined changes were also linearly increasing from never smokers to dysplasia + in situ carcinoma (P < 0.05 and P < 0.03). RAR-beta marker losses also increased from the first to the last group studied (P < 0.01), with a concomitant decrease in RAR-beta protein expression and correlated p53 increased immunoreactivity (P < 0.02). Losses at 3p14, 3p21, and P16 were frequent, but no significant differences between groups could be found. Unexpectedly, high constitutive homozygosity was observed near the RAR-alpha locus in squamous cell lung cancer cases. RARs/RXRs form homodimers or heterodimers involved in ligand binding. Their added alterations could result in a state of functional vitamin A deficiency in the affected bronchial cells. Further deletion events drawn from a limited repertoire of specific regions such as 3p14-21 and 9p21 could subsequently drive the deficient cells to invasive carcinoma.

Rapid mask prototyping for microfluidics.

With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks.

Light-induced retinal damage using different light sources, protocols and rat strains reveals LED phototoxicity.

To save energy, the European directives from the Eco-design of Energy Using Products (2005/32/CE) have recommended the replacement of incandescent lamps by more economic devices such as Light Emitting Diodes (LEDs). However, the emission spectrum of these devices is enriched in blue radiations, known to be potentially dangerous to the retina. Recent studies showed that light exposure contributes to the onset of early stages of age-related macular degeneration (AMD). Here, we investigate, in albinos and pigmented rats, the effects of different exposure protocols. Twenty-four hours exposure at high luminance was compared to a cyclic (dark/light) exposure at domestic levels for 1week and 1month, using different LEDs (Cold-white, blue and green), as well as fluorocompact bulbs and fluorescent tubes. The data suggest that the blue component of the white-LED may cause retinal toxicity at occupational domestic illuminance and not only in extreme experimental conditions, as previously reported. It is important to note that the current regulations and standards have been established on the basis of acute light exposure and do not take into account the effects of repeated exposure.

Colonic overexpression of the T-type calcium channel Cav 3.2 in a mouse model of visceral hypersensitivity and in irritable bowel syndrome patients.

BACKGROUND: Among the different mechanisms involved in irritable bowel syndrome (IBS) physiopathology, visceral hypersensitivity seems to play a key role. It involves sensitization of the colonic primary afferent fibers, especially through an overexpression of ion channels. The aims of this translational study were to investigate the colonic expression of Cav 3.2 calcium channels and their involvement in an animal model of colonic hypersensitivity, and to assess their expression in the colonic mucosa of symptomatic IBS patients. METHODS: This bench-to-bed study combined a preclinical experimental study on mice and a case-control clinical study. Preclinical studies were performed on wild-type and Cav 3.2-KO mice. Colonic sensitivity and Cav 3.2 expression were studied after a low-dose treatment of dextran sodium sulfate (DSS 0.5%). Regarding the clinical study, colonic biopsies were performed in 14 IBS patients and 16 controls during a colonoscopy to analyze the mucosal Cav 3.2 expression. KEY RESULTS: Wild-type, but not Cav 3.2-KO, mice developed visceral hypersensitivity without colonic inflammation, after 0.5% DSS treatment. A significant increase of Cav 3.2 mRNA (p = 0.04) was found in the colon of low-dose DSS-treated wild-type (WT) mice compared to their controls. In human colonic biopsies, the Cav 3.2 mRNA level was significantly higher in the IBS group compared to the control group (p = 0.01). The immunofluorescence staining revealed their protein expression in colonic mucosa, particularly in nerve fibers. CONCLUSIONS & INFERENCES: This translational study supports the involvement of the calcium channels Cav 3.2 in abdominal pain, as observed in IBS patients. It opens new therapeutic perspectives based on molecules specifically blocking these channels.

The association of serotype and pulsed-field gel electrophoresis genotype in isolates of Streptococcus pneumoniae isolated in Israel.

The relationship between Streptococcus pneumoniae isolates causing invasive infections in children admitted to a single center in central Israel was examined by pulsed-field gel electrophoresis (PFGE) and serotyping. Although there was a close correlation between serotype and PFGE clone, the genetic diversity varied by serotype, with some genotypes comprising multiple serotypes. Additionally, clones C and D were associated with higher penicillin minimum inhibitory concentrations. Serotyping alone may be insufficient for epidemiological mapping of pneumococcal isolates in the era of pneumococcal conjugate polysaccharide vaccines.

Down-regulation of peroxisome proliferator-activated receptor-gamma gene expression by sphingomyelins.

We recently demonstrated that the sphingomyelin (SM) content of adipocyte membranes was negatively correlated with the expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) in the subcutaneous adipose tissue of obese women with variable degrees of insulin resistance. We have now investigated whether SM really does have an impact on the expression of PPARgamma in 3T3-F442A adipocytes. Adding SM to the culture medium for 24 h caused a significant increase in SM content of adipocyte membranes and an acyl chain length-dependent decrease in the levels of PPARgamma mRNA and protein. The longer the acyl chain of the fatty acid of SM, the greater was the decrease in PPARgamma. These data suggest that the nature of the fatty acid is important in the regulation of PPARgamma by the SM pathway.

Vascular endothelial growth factor gene and protein: strong expression in thyroiditis and thyroid carcinoma.

Angiogenesis is implicated in several pathological conditions, such as inflammation and tumor growth. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent stimulator of endothelial cell proliferation in vitro and in vivo. The present work aimed to compare VEGF expression in human normal thyroid glands, thyroiditis tissue and thyroid carcinomas using immunohistochemistry and in situ hybridization (ISH). Both chronic lymphocytic thyroiditis and differentiated thyroid carcinomas were found to strongly express VEGF mRNA and encode larger amounts of VEGF than normal thyroid tissue as attested by a VEGF immunostaining score. In addition, tumor samples from patients with metastases showed a higher immunostaining score than their non-metastatic counterparts (P<0.05). Carcinomas with the greatest contents of VEGF mRNA and VEGF protein had the most intense mitogenic activity. Special focus on endothelial cells showed intense mitogenic activity in neoplastic tissues in contrast to the total quiescence of endothelial cells in non-tumoral tissues. An intense VEGF production by differentiated thyroid carcinoma, attested either by a higher immunostaining score or a strong VEGF mRNA expression using ISH, could be a promising marker of tumor aggressiveness and may also be useful as a predictor of metastatic potential.

A prospective study of fever and bacteremia after flexible fiberoptic bronchoscopy in children.

STUDY OBJECTIVES: To assess the incidence of fever and bacteremia after fiberoptic bronchoscopy in immunocompetent children. DESIGN: Prospective study. PATIENTS: Immunocompetent children undergoing fiberoptic bronchoscopy between January 1997 and June 1998. MEASUREMENTS AND RESULTS: Ninety-one children were included in the study. Forty-four children (48%) developed fever within 24 h following bronchoscopy. Bacteremia was not detected in any of the cases at the time of the fever. Children who developed fever were younger than those who remained afebrile (mean age, 2.4 +/- 3.6 years vs 4.2 +/- 3.7 years; p = 0.025). In the fever group, 66% of the bronchoscopies were considered abnormal, compared to 45% in the nonfever group (p = 0.04). Of the fever group, 40.5% of BAL fluid cultures had significant bacterial growth, significantly higher compared to the nonfever group (13.2%; p = 0.006). Of the 80 patients in whom BAL was performed, fever occurred in 52.5% compared to only 18.2% in those who did not have BAL (p = 0.03). BAL fluid content of cell count, lipid-laden macrophages, and interleukin-8 were not significantly different in both groups. In a logistic regression analysis, the significant predictors for developing fever were positive bacterial culture (relative risk, 5.1; 95% confidence interval, 1.6 to 16.4; p = 0.007) and abnormal bronchoscopic findings (relative risk, 3.1, 95% confidence interval, 1.2 to 8.3; p = 0.02). When age < 2 years was included in the model, this factor became highly significant (relative risk, 5.01; 95% confidence interval, 1.83 to 13.75; p < 0.002). CONCLUSIONS: Fever following fiberoptic bronchoscopy is a common event in immunocompetent children and is not associated with bacteremia. Risks to develop this complication are age < 2 years, positive bacterial cultures in BAL fluid, and abnormal bronchoscopic findings.

Primary pulmonary hypertension in Israel: a national survey.

OBJECTIVES: To characterize the incidence of patients with primary pulmonary hypertension (PPH) in Israel and their outcomes. METHODS: We have evaluated retrospectively all the patients in Israel in whom PPH was diagnosed between the years 1988 and 1997. We looked at medical history, hemodynamic data, pulmonary function and gas exchange, and demographic variables. Patients were followed up for survival until November 1997. Life table analysis and Kaplan-Meier statistics were used to estimate the overall survival distribution. Regression analysis was used to examine the relations between survival and selected variables. RESULTS: Overall, we found 44 patients with PPH. The estimated incidence of PPH in Israel is 1.4 new cases per year per million population. The mean (+/- SD) age at diagnosis was 43 +/- 13 years. In the Jewish population, PPH was more frequent among immigrants from Europe and the United States. The mean interval from the onset of symptoms to diagnosis was 3 years (median, 2 years). The median survival time was 4 years. The 1-year, 3-year, and 5-year survival rates were 82%, 57%, and 43%, respectively. The major variables influencing the survival rate were the following: interval from symptom onset to diagnosis; and hemodynamic measurements (ie, mean pulmonary artery pressure, mean right atrial pressure, and cardiac index). In comparison to rates discerned from the National Institutes of Health registry data, the survival rate in Israel is somewhat better and prognosis is influenced by similar hemodynamic variables. CONCLUSION: PPH is a rare and fatal disease in Israel. New therapeutic modalities such as prostacyclin therapy and lung transplantation may improve survival among patients with this malignant disease.